Methionine (Met)-enkephalin content was examined in several areas of the brain of ethanol-dependent rats, including the frontal cortex, caudate nucleus, hypothalamus, medulla oblongata and pons. Physical dependence on ethanol was induced over a 4 day period with daily 9-13 g/kg doses of ethanol delivered in 4-6 fractions. Met-enkephalin was selectively reduced in the frontal cortex of animals undergoing an ethanol withdrawal syndrome, but not in dependent-intoxicated animals. No alternations in Met-enkephalin were observed in the other areas of the brain studied. Single doses of ethanol and malnutrition had no effect on Met-enkephalin content. The data suggest that a reduction in cerebral Met-enkephalin content may contribute to the expression of ethanol withdrawal syndrome.